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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
18
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pubmed:dateCreated |
2011-5-2
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pubmed:abstractText |
Progranulin (GRN) haploinsufficiency is a frequent cause of familial frontotemporal dementia, a currently untreatable progressive neurodegenerative disease. By chemical library screening, we identified suberoylanilide hydroxamic acid (SAHA), a Food and Drug Administration-approved histone deacetylase inhibitor, as an enhancer of GRN expression. SAHA dose-dependently increased GRN mRNA and protein levels in cultured cells and restored near-normal GRN expression in haploinsufficient cells from human subjects. Although elevation of secreted progranulin levels through a post-transcriptional mechanism has recently been reported, this is, to the best of our knowledge, the first report of a small molecule enhancer of progranulin transcription. SAHA has demonstrated therapeutic potential in other neurodegenerative diseases and thus holds promise as a first generation drug for the prevention and treatment of frontotemporal dementia.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
1083-351X
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pubmed:author |
pubmed-author:AlmeidaSandraS,
pubmed-author:CenikBasarB,
pubmed-author:CoppolaGiovanniG,
pubmed-author:CoughlinSarah ESE,
pubmed-author:DeweyColleen MCM,
pubmed-author:DriesDaniel RDR,
pubmed-author:FareseRobert VRVJr,
pubmed-author:GaoFen-BiaoFB,
pubmed-author:GeschwindDaniel HDH,
pubmed-author:HerzJoachimJ,
pubmed-author:LeeSuzee ESE,
pubmed-author:MillerBruce LBL,
pubmed-author:NiuWenzeW,
pubmed-author:PosnerBruce ABA,
pubmed-author:SephtonChantelle FCF,
pubmed-author:WeiShuguangS,
pubmed-author:XianXundeX,
pubmed-author:YuGangG,
pubmed-author:YuKimberleyK
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pubmed:issnType |
Electronic
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pubmed:day |
6
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pubmed:volume |
286
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
16101-8
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pubmed:meshHeading |
pubmed-meshheading:21454553-Dose-Response Relationship, Drug,
pubmed-meshheading:21454553-Frontotemporal Dementia,
pubmed-meshheading:21454553-HEK293 Cells,
pubmed-meshheading:21454553-Histone Deacetylase Inhibitors,
pubmed-meshheading:21454553-Humans,
pubmed-meshheading:21454553-Hydroxamic Acids,
pubmed-meshheading:21454553-Intercellular Signaling Peptides and Proteins,
pubmed-meshheading:21454553-Transcription, Genetic,
pubmed-meshheading:21454553-Up-Regulation
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pubmed:year |
2011
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pubmed:articleTitle |
Suberoylanilide hydroxamic acid (vorinostat) up-regulates progranulin transcription: rational therapeutic approach to frontotemporal dementia.
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pubmed:affiliation |
Department of Neuroscience, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390-9111, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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